The past year has seen the discovery of three major new synthetic methods: (1) The totally specific electrophilic dehalogenation of 2,4- dihaloimidazoles to give 2-haloimidazoles, thus making 2-iodohistidine and 2-iodohistamine readily available for antimalarial studies; (2) the use of transient ylid-carbenes to provide a route to 2-X-imidazoles not otherwise accessible; (3) the development of cyclic urea derivatives of histidine and histamine in opening totally new directions for achieving regiospecific ring substitution in bioimidazoles. Parallel studies are under way with cyclic sulfones of these imidazoles and appear likely to provide extremely useful protection for histidine in peptide synthesis. This method provides the first practical route to mono- and dichlorohistidine. We have now demonstrated that 2-nitroimidazoles are far more reactive chemically than supposed, and that loss of the nitro group follows both ionic and radical pathways. These results provide the first support for our theory that 2-nitroimidazoles act as radiosensitizers and cytotoxic agents by affinity alkylation with imidazole radicals, and not by the generally assumed reduction of the nitro group to the hydroxylamine stage. Perfluoroalkylimidazoles have been found to undergo facile nitration and halogenation without destruction; therefore, methods are now available to prepare photosensitive ligands (azido, diazo) and ligands labeled with radioiodine. Perfluoroalkylimidazoles have attracted considerable attention because of their utility in providing lipophilic sites in medicinal agents and because of their potential use as "ligand-activated affinity labels." These compounds are converted by mild base into perfluoroalkyl ketones, which have such reactive carbonyl groups that they may serve as irreversible affinity labels for bioimidazole-binding sites in enzymes and in receptors. Perfluoroalkylimidazoles are prepared by photochemical reaction or by condensation of the imidazole (or mercaptoimidazole) with bis(perfluoroalkanoyl)peroxides.